We have previously reported that a triple-helical, collagen-related peptide (CRP; also known as CRP-XL) containing a glycine-proline-hydroxyproline (GPP*) repeat motif and cross-linked through cysteine residues at its N-terminus and C-terminus is a powerful stimulus of platelet aggregation and secretion through the surface receptor glycoprotein VI (GPVI). The activation of platelets is associated with tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase C γ2 (PLCγ2). We now report that the non-cross-linked backbone of CRP, monomeric CRP (mCRP), stimulates the tyrosine phosphorylation of Syk and PLCγ2 in platelets and induces the weak secretion of [3H]5-hydroxytryptamine ([3H]5-HT) and aggregation. The action of mCRP does not seem to be due to spontaneous cross-linking, because alkylation of the cysteine residues leads to an increase in activity. The tripeptide backbone of CRP, GPP*10 (in which P* represents hydroxyproline) also stimulates platelet shape change and the weak tyrosine phosphorylation of Syk and PLCγ2, but is unable to induce aggregation or secretion. The monomeric peptides partly inhibit the release of [3H]5-HT by CRP, suggesting that they are partial agonists of the collagen receptor GPVI. These results demonstrate that GPP* present as a repeat motif is sufficient to activate the platelet collagen receptor GPVI but that the cross-linking of monomers brings about an increase in activity.
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April 1999
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Research Article|
April 08 1999
Monomeric (glycine-proline-hydroxyproline)10 repeat sequence is a partial agonist of the platelet collagen receptor glycoprotein VI
Judith ASSELIN;
Judith ASSELIN
*Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
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C. Graham KNIGHT;
C. Graham KNIGHT
†Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K.
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Richard W. FARNDALE;
Richard W. FARNDALE
†Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K.
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Michael J. BARNES;
Michael J. BARNES
†Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, U.K.
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Steve P. WATSON
Steve P. WATSON
1
*Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
1To whom correspondence should be addressed (e-mail steve.watson@pharm.ox.ac.uk).
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Publisher: Portland Press Ltd
Received:
May 26 1998
Revision Received:
January 04 1999
Accepted:
February 08 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 339 (2): 413–418.
Article history
Received:
May 26 1998
Revision Received:
January 04 1999
Accepted:
February 08 1999
Citation
Judith ASSELIN, C. Graham KNIGHT, Richard W. FARNDALE, Michael J. BARNES, Steve P. WATSON; Monomeric (glycine-proline-hydroxyproline)10 repeat sequence is a partial agonist of the platelet collagen receptor glycoprotein VI. Biochem J 15 April 1999; 339 (2): 413–418. doi: https://doi.org/10.1042/bj3390413
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